NEW YORK (Reuters Health) - Various combinations of nutritional supplementation over more than five years do not appear to affect long-term total and cancer mortality, according to results from the Linxian Nutrition Intervention Trial (NIT).

"The NIT General Population Trial was one of the few randomized clinical trials to report that supplementation with a specific vitamin and mineral combination (selenium, vitamin E, and beta-carotene) could reduce the risk of total mortality at the end of the 5.25-year supplementation period," said Dr. Christian C. Abnet from the National Cancer Institute, in Rockville, Maryland.

"In 2009, we reported that this reduced risk extended up to 10 years after the end of supplementation. In the current work, we find that the protective effect of the intervention began to fade and risk of mortality in the supplemented group has now returned to the baseline," he told Reuters Health by email.

Dr. Abnet and colleagues detail the findings after more than 588,000 person-years of follow-up for an additional 25 years after study completion in a paper online April 3 in the Journal of the National Cancer Institute.

For the 30-year follow-up overall, there were no differences in total mortality between the intervention and nonintervention groups for any of the nutritional supplement combinations.

In this extended analysis, retinol/zinc appeared to provide some protection against death from non-upper gastrointestinal cancer while slightly increasing the risk of esophageal cancer death; riboflavin/niacin afforded some protection against esophageal cancer death; and vitamin C/molybdenum reduced the risk of death from gastric cardia cancer and cancer overall.

Overall, there were no significant differences between sexes for the intervention effects on total mortality and cancer mortality.

There were, however, differences by age. Persons younger than 55 years at baseline had lower death rates from non-upper gastrointestinal cancers with retinol/zinc, fewer stroke deaths with vitamin C/molybdenum and fewer gastric cardia cancer deaths with selenium/vitamin E/beta-carotene.

Persons aged 55 years or older at entry, on the other hand, had increased death rates from esophageal cancer and gastric cardia cancer and total cancer mortality with vitamin C/molybdenum and increased death rates from esophageal cancer with selenium/vitamin E/beta-carotene.

"Our trial was conducted in a nutritionally deprived population, and there is good reason to believe that the effects we found are specific to our population or other similarly deficient groups," Dr. Abnet said. "We should not interpret these findings to be relevant to populations that consume varied diets and lack these specific deficiencies."

"For the target population we learned that even with 5 years of supplementation, we should not expect the protective effects of these supplements to last a lifetime," he said.

Dr. Alison Mondul of the University of Michigan, in Ann Arbor, has researched various aspects of nutrition and their relationship to cancer mortality. She told Reuters Health by email, "Supplements are clearly beneficial for some people, but might actually be harmful for others, as was seen particularly for older people for certain outcomes in this study and which has been reported in other studies mentioned in the article. We are still in the process of figuring out who should take which ones, for how long, and how much they should take."

"We should start to think of supplements like any other pill people might take: they shouldn't be just given to everyone and more isn't necessarily better," she said. "The idea that, at worst, supplements do nothing seems not to be true."

"People with adequate nutrition likely do not need to take nutritional supplements, and giving them in large doses, particularly to older patients, may actually cause harm," Dr. Mondul concluded. "In addition, any effect of supplements likely doesn't continue for more than 10 years after people stop taking them."